ABSTRACT People who inject drugs (PWID) often do not receive evidence-based HIV prevention interventions, including syringe service programs (SSP), medications for opioid use disorder (MOUD) and pre-exposure prophylaxis (PrEP). This is an urgent problem in Connecticut and Massachusetts. Interventions that address individual and structural barriers are needed. Furthermore, since PWID often do not receive routine medical care, it is important to engage them in care in community-based settings. Although contingency management (CM) (i.e., use of tangible rewards to incentivize verifiable behavior change) can be effective to address substance use and infectious disease prevention and treatment, it has not been studied for PrEP among PWID. CM may not be uniformly effective as some individuals may need additional intervention, such as PrEP navigation, to overcome individual or structural barriers to receiving HIV prevention interventions. Stepped care strategies offer a solution as they are adaptive to individuals? response (e.g. stepped care) to meet individual needs while optimizing resources. We, therefore, propose a randomized controlled trial of 526 PrEP-eligible PWID in partnership with opioid treatment programs, a harm reduction agency and AIDS service organization to evaluate the impact of CM with stepped care as needed to include PrEP navigation (?CM2PN?) vs. treatment as usual (?TAU?). Participants randomized to CM2PN will receive prize-based CM sessions over 9 sessions to reward progress towards PrEP initiation adherence, engagement in MOUD and engagement in SSP and other risk reduction activities. Individuals who do not have high levels of PrEP adherence by week 12 based on self- report and confirmed by point-of-care urine testing, will be ?stepped up? to receive PrEP navigation over 5 sessions. PrEP navigation will be informed by Project INFORM and ARTAS, tailored specifically for PWID and grounded in motivation interviewing principles. The intervention, CM2PN, will be delivered by trained PrEP navigators. TAU includes a pamphlet on PrEP and information on ways to access other relevant care (e.g., MOUD). The primary outcome will be sustained PrEP adherence assessed by dried blood spot testing to evaluate cumulative dosing over 6-8 weeks. Our specific aims are to compare the effectiveness of CM2PN vs. TAU on: 1) on sustained PrEP adherence at 24 weeks; 2) HIV risk behaviors; engagement in opioid use disorder-related care (SSP, MOUD) and extra-medical opioid use; and (exploratory) STI and HIV acquisition; and 3) among PrEP navigators, front-line providers and staff, and leadership at each site, conduct an implementation focused-process evaluation of CM2PN. Our team has expertise in integrating HIV and opioid use disorder-related care, CM, clinicals trials with adaptive designs, community-engaged research and implementation science. Innovative aspects include multi-target CM for PWID for PrEP; stepped care design; academic-community-public health partnership to expand reach, impact and data capture. Study is of high impact as CM2PN holds exceptional promise for promoting HIV prevention among PWID globally.